Observation and/or Combination Chemotherapy After Surgery or Biopsy in Treating Young Patients With Extracranial Germ Cell Tumors

Sponsor

Children's Cancer and Leukaemia Group (Other)

Overall Status

Unknown status

CT.gov ID

NCT00274950

Collaborator

(none)

105

Enrollment

Locations

5.3

Patients Per Site

Study Details

Study Description

Brief Summary

RATIONALE: Sometimes, after surgery, the tumor may not need additional treatment until it progresses. In this case, observation may be sufficient. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving combination chemotherapy after surgery may kill any remaining tumor cells.

PURPOSE: This phase III trial is studying how well observation and/or combination chemotherapy works after surgery or biopsy in treating young patients with extracranial germ cell tumors.

Condition or Disease	Intervention/Treatment	Phase
Childhood Germ Cell Tumor Extragonadal Germ Cell Tumor Ovarian Cancer	Biological: bleomycin sulfate Drug: carboplatin Drug: cisplatin Drug: etoposide Drug: ifosfamide Drug: vinblastine sulfate Procedure: adjuvant therapy Procedure: conventional surgery	Phase 3

Detailed Description

OBJECTIVES:

Stratify and reduce treatment for pediatric patients with extracranial germ cell tumors while maintaining event-free survival.
Treat newly diagnosed patients with extracranial germ cell tumors requiring chemotherapy with a carboplatin-based strategy.
Develop a common strategy for the treatment of patients with recurrent or progressive extracranial germ cell tumors.
Register all cases of mature and immature teratoma.
Develop a common strategy for the management of immature and mature teratoma, including follow-up strategies to permit early detection of yolk sac recurrence.

OUTLINE: This is a multicenter study.

Patients who have not had prior biopsy or surgical resection undergo biopsy (if feasible) or surgical resection. Patients with mature or immature teratoma undergo observation. These patients who relapse (i.e., tumor regrowth) may undergo further surgical resection unless tumor markers are significantly elevated. If the tumor markers are significantly elevated, these patients proceed to JEB chemotherapy according to risk group. Patients with all other malignant germ cell tumors are assigned to 1 of 3 treatment groups according to risk.

Low-risk group: Patients with normal tumor markers undergo observation. Patients with rising tumor markers only AND no imageable tumor proceed to treatment as in the intermediate-risk group. Patients with rising tumor markers AND/OR imageable tumor are considered to have relapsed and proceed to treatment as in the intermediate- or high-risk group.
Intermediate-risk group: Patients receive JEB chemotherapy comprising etoposide IV over 4 hours on days 1-3, carboplatin IV over 1 hour on day 2, and bleomycin IV over 30 minutes on day 3. Treatment repeats every 21 days for 4 courses. Patients with residual tumors after completion of chemotherapy may undergo second-look surgery.
High-risk group: Patients receive JEB chemotherapy as in the intermediate-risk group for 6 courses. Patients with residual tumors after completion of chemotherapy may undergo second-look surgery.
Relapse therapy: Patients in the intermediate- or high-risk group who relapse after completion of JEB chemotherapy receive vinblastine IV on days 1 and 2, ifosfamide IV over 1 hour on days 1-5, and cisplatin IV on days 1-5. Treatment repeats every 21 days for 6 courses.

PROJECTED ACCRUAL: A total of 105 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

105 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Protocol for the Treatment of Extracranial Germ Cell Tumours in Children and Adolescents (GC III)

Study Start Date :

May 1, 2005

Anticipated Primary Completion Date :

May 1, 2010

Outcome Measures

Primary Outcome Measures

Event-free survival []
Continuation of treatment []
Development of common and follow-up strategies []
Registration of all cases of mature and immature teratoma []

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically* proven extracranial malignant germ cell tumor (GCT), including mature/immature teratoma, with or without elevated alpha-fetoprotein (AFP) or human chorionic gonadotropin (HCG) levels
Newly diagnosed disease
Patients with relapsed or progressive extracranial malignant GCT allowed if previously treated with carboplatin, etoposide, and bleomycin (JEB) chemotherapy
Patients relapsing following JEB are eligible for the study relapse strategy NOTE: *Patients with unequivocally raised AFP/HCG whose risk of biopsy is felt to be high can be diagnosed by clinical grounds, imaging, and markers
No intracranial GCTs

PATIENT CHARACTERISTICS:

Neutrophil count ≥ 1,000/mm^3
Platelet count ≥ 100,000/mm^3
Bilirubin ≤ 2 times upper limit of normal (ULN)
ALT ≤ 3 times ULN
Not pregnant or nursing

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior chemotherapy other than JEB

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Our Lady's Hospital for Sick Children Crumlin	Dublin		Ireland	12
2	Birmingham Children's Hospital	Birmingham	England	United Kingdom	B4 6NH
3	Institute of Child Health at University of Bristol	Bristol	England	United Kingdom	BS2 8AE
4	Addenbrooke's Hospital	Cambridge	England	United Kingdom	CB2 2QQ
5	Leeds Cancer Centre at St. James's University Hospital	Leeds	England	United Kingdom	LS9 7TF
6	Leicester Royal Infirmary	Leicester	England	United Kingdom	LE1 5WW
7	Royal Liverpool Children's Hospital, Alder Hey	Liverpool	England	United Kingdom	L12 2AP
8	Royal London Hospital	London	England	United Kingdom	E1 1BB
9	Great Ormond Street Hospital for Children	London	England	United Kingdom	WC1N 3JH
10	Royal Manchester Children's Hospital	Manchester	England	United Kingdom	M27 4HA
11	Sir James Spence Institute of Child Health at Royal Victoria Infirmary	Newcastle-Upon-Tyne	England	United Kingdom	NE1 4LP
12	Queen's Medical Centre	Nottingham	England	United Kingdom	NG7 2UH
13	Children's Hospital - Sheffield	Sheffield	England	United Kingdom	S10 2TH
14	Southampton General Hospital	Southampton	England	United Kingdom	SO16 6YD
15	Royal Marsden - Surrey	Sutton	England	United Kingdom	SM2 5PT
16	Royal Belfast Hospital for Sick Children	Belfast	Northern Ireland	United Kingdom	BT12 6BE
17	Royal Aberdeen Children's Hospital	Aberdeen	Scotland	United Kingdom	AB25 2ZG
18	Royal Hospital for Sick Children	Edinburgh	Scotland	United Kingdom	EH9 1LF
19	Royal Hospital for Sick Children	Glasgow	Scotland	United Kingdom	G3 8SJ
20	Childrens Hospital for Wales	Cardiff	Wales	United Kingdom	CF14 4XW